Search Results (5)

Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. Objective: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-β/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). Materials and Methods: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-β/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. Results: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-β/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. Conclusions: PPAR-γ2 rs1801282 and PPAR-β/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved. Full article

Background: Thiazolidinediones (TZDs) are a type of oral drug that are utilized for the treatment of type 2 diabetes mellitus (T2DM). They function by acting as agonists for a nuclear transcription factor known as peroxisome proliferator-activated receptor-gamma (PPAR-γ). TZDs, such as pioglitazone and rosiglitazone, help enhance the regulation of metabolism in individuals with T2DM by improving their sensitivity to insulin. Previous studies have suggested a relationship between the therapeutic efficacy of TZDs and the PPARG Pro12Ala polymorphism (C > G, rs1801282). However, the small sample sizes of these studies may limit their applicability in clinical settings. To address this limitation, we conducted a meta-analysis assessing the influence of the PPARG Pro12Ala polymorphism on the responsiveness of TZDs. Method: We registered our study protocol with PROSPERO, number CRD42022354577. We conducted a comprehensive search of the PubMed, Web of Science, and Embase databases, including studies published up to August 2022. We examined studies investigating the association between the PPARG Pro12Ala polymorphism and metabolic parameters such as hemoglobin A_1C (HbA_1C), fasting plasma glucose (FPG), triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and total cholesterol (TC). The mean difference (MD) and 95% confidence intervals (CIs) between pre- and post-drug administration were evaluated. The quality of the studies included in the meta-analysis was assessed by using the Newcastle–Ottawa Scale (NOS) tool for cohort studies. Heterogeneity across studies was assessed by using the I² value. An I² value greater than 50% indicated substantial heterogeneity, and a random-effects model was used for meta-analysis. If the I² value was below 50%, a fixed-effects model was employed instead. Both Begg’s rank correlation test and Egger’s regression test were performed to detect publication bias, using R Studio software. Results: Our meta-analysis incorporated 6 studies with 777 patients for blood glucose levels and 5 studies with 747 patients for lipid levels. The included studies were published between 2003 and 2016, with the majority involving Asian populations. Five of the six studies utilized pioglitazone, while the remaining study employed rosiglitazone. The quality scores, as assessed with the NOS, ranged from 8 to 9. Patients carrying the G allele exhibited a significantly greater reduction in HbA_1C (MD = −0.3; 95% CI = −0.55 to −0.05; p = 0.02) and FPG (MD = −10.91; 95% CI = −19.82 to −2.01; p = 0.02) levels compared to those with the CC genotype. Furthermore, individuals with the G allele experienced a significantly larger decrease in TG levels than those with the CC genotype (MD = −26.88; 95% CI = −41.30 to −12.46; p = 0.0003). No statistically significant differences were observed in LDL (MD = 6.69; 95% CI = −0.90 to 14.29; p = 0.08), HDL (MD = 0.31; 95% CI = −1.62 to 2.23; p = 0.75), and TC (MD = 6.4; 95% CI = −0.05 to 12.84; p = 0.05) levels. No evidence of publication bias was detected based on Begg’s test and Egger’s test results. Conclusions: This meta-analysis reveals that patients with the Ala12 variant in the PPARG Pro12Ala polymorphism are more likely to exhibit positive responses to TZD treatment in terms of HbA_1C, FPG, and TG levels compared to those with the Pro12/Pro12 genotype. These findings suggest that genotyping the PPARG Pro12Ala in diabetic patients may be advantageous for devising personalized treatment strategies, particularly for identifying individuals who are likely to respond favorably to TZDs. Full article

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation. Full article

Background: So far, numerous meta-analyses have been published regarding the correlation between peroxisome proliferator-activated receptor gamma (PPARG) proline 12 alanine (Pro12Ala) gene polymorphism and chronic kidney disease (CKD); however, the results appear to be contradictory. Hence, this study is formulated with the objective of using existing meta-analysis data together with our research population to study the correlation between PPARG Pro12Ala gene polymorphism and CKD and evaluate whether an accurate result can be obtained. Methods: First, literature related to CKD and PPARG Pro12Ala available on the PubMed and EMBASE databases up to December 2016 was gathered from 20 publications. Then, the gathered results were combined with our case-control study of 1693 enrolled subjects and a trial sequential analysis (TSA) was performed to verify existing evidence and determine whether a firm conclusion can be drawn. Results: The TSA results showed that the cumulative sample size for the Asian sample was 6078 and was sufficient to support a definite result. The results of this study confirmed that there is no obvious correlation between PPARG Pro12Ala and CKD for Asians (OR = 0.82 (95% CI = 0.66–1.02), I² = 63.1%), but this was not confirmed for Caucasians. Furthermore, the case-control sample in our study was shown to be the key for reaching this conclusion. Conclusions: The meta-analysis results of this study suggest no significant correlation between PPARG Pro12Ala gene polymorphism and CKD for Asians after adding our samples, but not for Caucasian. Full article

Background: The peroxisome proliferator-activated receptors (PPARA, PPARG, PPARD) and their transcriptional coactivators’ (PPARGC1A, PPARGC1B) gene polymorphisms have been associated with muscle morphology, oxygen uptake, power output and endurance performance. The purpose of this review is to determine whether the PPARs and/or their coactivators’ polymorphisms can predict the training response to specific training stimuli. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses, a literature review has been run for a combination of PPARs and physical activity key words. Results: All ten of the included studies were performed using aerobic training in general, sedentary or elderly populations from 21 to 75 years of age. The non-responders for aerobic training (VO₂peak increase, slow muscle fiber increase and low-density lipoprotein decrease) are the carriers of PPARGC1A rs8192678 Ser/Ser. The negative responders for aerobic training (decrease in VO₂peak) are carriers of the PPARD rs2267668 G allele. The negative responders for aerobic training (decreased glucose tolerance and insulin response) are subjects with the PPARG rs1801282 Pro/Pro genotype. The best responders to aerobic training are PPARGC1A rs8192678 Gly/Gly, PPARD rs1053049 TT, PPARD rs2267668 AA and PPARG rs1801282 Ala carriers. Conclusions: The human response for aerobic training is significantly influenced by PPARs’ gene polymorphism and their coactivators, where aerobic training can negatively influence glucose metabolism and VO₂peak in some genetically-predisposed individuals. Full article